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Background: Preterm prelabor rupture of membranes (PPROM) before 34 weeks of gestation complicates 1% of pregnancies and accounts for one-third of preterm births. International guidelines recommend expectant management, along with antenatal steroids before 34 weeks and antibiotics. Up-to-date evidence about the risks and benefits of administering tocolysis after PPROM, however, is lacking. In theory, reducing uterine contractility could delay delivery and reduce the risks of prematurity and its adverse short- and long-term consequences, but it might also prolong fetal exposure to inflammation, infection, and acute obstetric complications, potentially associated with neonatal death or long-term sequelae. The primary objective of this study is to assess whether short-term (48 h) tocolysis reduces perinatal mortality/morbidity in PPROM at 22 to 33 completed weeks of gestation.Methods: A randomized, double-blind, placebo-controlled, superiority trial will be performed in 29 French maternity units. Women with PPROM between 220/7 and 336/7 weeks of gestation, a singleton pregnancy, and no condition contraindicating expectant management will be randomized to receive a 48-hour oral treatment by either nifedipine or placebo (1:1 ratio). The primary outcome will be the occurrence of perinatal mortality/morbidity, a composite outcome including fetal death, neonatal death, or severe neonatal morbidity before discharge. If we assume an alpha-risk of 0.05 and beta-risk of 0.20 (i.e., a statistical power of 80%), 702 women (351 per arm) are required to show a reduction of the primary endpoint from 35% (placebo group) to 25% (nifedipine group). We plan to increase the required number of subjects by 20%, to replace any patients who leave the study early. The total number of subjects required is thus 850. Data will be analyzed by the intention-to-treat principle.Discussion: This trial will inform practices and policies worldwide. Optimized prenatal management to improve the prognosis of infants born preterm could benefit about 50,000 women in the European Union and 40,000 in the United States each year.Trial Registration: ClinicalTrials.gov identifier: NCT03976063 (registration date June 5, 2019). [ABSTRACT FROM AUTHOR]

Background: The trematode parasite Fasciola hepatica causes important economic losses in ruminants worldwide. Current spatial distribution models do not provide sufficient detail to support farm-specific control strategies. A technology to reliably assess the spatial distribution of intermediate host snail habitats on farms would be a major step forward to this respect. The aim of this study was to conduct a longitudinal field survey in Flanders (Belgium) to (i) characterise suitable small water bodies (SWB) for Galba truncatula and (ii) describe the population dynamics of G. truncatula. Methods: Four F. hepatica-infected farms from two distinct agricultural regions were examined for the abundance of G. truncatula from the beginning (April 2012) until the end (November 2012) of the grazing season. Per farm, 12 to 18 SWB were selected for monthly examination, using a 10 m transect analysis. Observations on G. truncatula abundance were coupled with meteorological and (micro-)environmental factors and the within-herd prevalence of F. hepatica using simple comparison or negative binomial regression models. Results: A total of 54 examined SWB were classified as a pond, ditch, trench, furrow or moist area. G. truncatula abundance was significantly associated with SWB-type, region and total monthly precipitation, but not with monthly temperature. The clear differences in G. truncatula abundance between the 2 studied regions did not result in comparable differences in F. hepatica prevalence in the cattle. Exploration of the relationship of G. truncatula abundance with (micro)-environmental variables revealed a positive association with soil and water pH and the occurrence of Ranunculus sp. and a negative association with mowed pastures, water temperature and presence of reed-like plant species. Conclusions: Farm-level predictions of G. truncatula risk and subsequent risk for F. hepatica occurrence would require a rainfall, soil type (representing the agricultural region) and SWB layer in a geographic information system. While rainfall and soil type information is easily accessible, the recent advances in very high spatial resolution cameras carried on board of satellites, planes or drones should allow the delineation of SWBs in the future. [ABSTRACT FROM AUTHOR]

Background: Despite the known importance of somatic cells for oocyte developmental competence acquisition, the overall mechanisms underlying the acquisition of full developmental competence are far from being understood, especially in non-mammalian species. The present work aimed at identifying key molecular signals from somatic origin that would be shared by vertebrates. Results: Using a parallel transcriptomic analysis in 4 vertebrate species - a teleost fish, an amphibian, and two mammals - at similar key steps of developmental competence acquisition, we identified a large number of species-specific differentially expressed genes and a surprisingly high number of orthologous genes exhibiting similar expression profiles in the 3 tetrapods and in the 4 vertebrates. Among the evolutionary conserved players participating in developmental competence acquisition are genes involved in key processes such as cellular energy metabolism, cell-to-cell communications, and meiosis control. In addition, we report many novel molecular actors from somatic origin that have never been studied in the vertebrate ovary. Interestingly, a significant number of these new players actively participate in Drosophila oogenesis. Conclusions: Our study provides a comprehensive overview of evolutionary-conserved mechanisms from somatic origin participating in oocyte developmental competence acquisition in 4 vertebrates. Together our results indicate that despite major differences in ovarian follicular structure, some of the key players from somatic origin involved in oocyte developmental competence acquisition would be shared, not only by vertebrates, but also by metazoans. The conservation of these mechanisms during vertebrate evolution further emphasizes the important contribution of the somatic compartment to oocyte quality and paves the way for future investigations aiming at better understanding what makes a good egg. [ABSTRACT FROM AUTHOR]

Background: Surveillance for bovine genetic diseases in Denmark identified a hitherto unreported congenital syndrome occurring among progeny of a Holstein sire used for artificial breeding. A genetic aetiology due to a dominant inheritance with incomplete penetrance or a mosaic germline mutation was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause. Results: Seven malformed calves were submitted examination. All cases shared a common morphology with the most striking lesions being severe facial dysplasia and complete prolapse of the eyes. Consequently the syndrome was named facial dysplasia syndrome (FDS). Furthermore, extensive brain malformations, including microencephaly, hydrocephalus, lobation of the cerebral hemispheres and compression of the brain were present. Subsequent data analysis of progeny of the sire revealed that around 0.5% of his offspring suffered from FDS. High density single nucleotide polymorphism (SNP) genotyping data of the seven cases and their parents were used to map the defect in the bovine genome. Significant genetic linkage was obtained for three regions, including chromosome 26 where whole genome sequencing of a case-parent trio revealed two de novo variants perfectly associated with the disease: an intronic SNP in the DMBT1 gene and a single non-synonymous variant in the FGFR2 gene. This FGFR2 missense variant (c.927G>T) affects a gene encoding a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and across species. It is predicted to change an evolutionary conserved tryptophan into a cysteine residue (p.Trp309Cys). Both variant alleles were proven to result from de novo mutation events in the germline of the sire. Conclusions: FDS is a novel genetic disorder of Holstein cattle. Mutations in the human FGFR2 gene are associated with various dominant inherited craniofacial dysostosis syndromes. Given the phenotypic similarities in FDS affected calves, the genetic mapping and absence of further high impact variants in the critical genome regions, it is highly likely that the missense mutation in the FGFR2 gene caused the FDS phenotype in a dominant mode of inheritance. [ABSTRACT FROM AUTHOR]

Background Gene regulatory processes are largely resulting from binding of transcription factors to specific genomic targets. Leucine-responsive Regulatory Protein (Lrp) is a prevalent transcription factor family in prokaryotes, however, little information is available on biological functions of these proteins in archaea. Here, we study genome-wide binding of the Lrp-like transcription factor Ss-LrpB from Sulfolobus solfataricus. Results Chromatin immunoprecipitation in combination with DNA microarray analysis (ChIP-chip) has revealed that Ss-LrpB interacts with 36 additional loci besides the four previously identified local targets. Only a subset of the newly identified binding targets, concentrated in a highly variable IS-dense genomic region, is also bound in vitro by pure Ss-LrpB. There is no clear relationship between the in vitro measured DNA-binding specificity of Ss-LrpB and the in vivo association suggesting a limited permissivity of the crenarchaeal chromatin for transcription factor binding. Of 37 identified binding regions, 29 are co-bound by LysM, another Lrp-like transcription factor in S. solfataricus. Comparative gene expression analysis in an Ss-lrpB mutant strain shows no significant Ss-LrpB-mediated regulation for most targeted genes, with exception of the CRISPR B cluster, which is activated by Ss-LrpB through binding to a specific motif in the leader region. Conclusions The genome-wide binding profile presented here implies that Ss-LrpB is associated at additional genomic binding sites besides the local gene targets, but acts as a specific transcription regulator in the tested growth conditions. Moreover, we have provided evidence that two Lrp-like transcription factors in S. solfataricus, Ss-LrpB and LysM, interact in vivo. [ABSTRACT FROM AUTHOR]

Background: From a health promotion perspective, the use of dietary indices is preferred above single nutrients and foods to evaluate diet quality. Longitudinal research about the association between dietary indices and respectively anthropometric parameters and blood lipids is lacking. The aim of this study was to investigate the longitudinal association between three dietary indices (Healthy Eating Index-2010 (HEI), Mediterranean Diet Score (MDS) and Diet Quality Index (DQI)) and respectively anthropometric parameters and blood lipids. Methods: A three day diet record was completed by 373 men and 197 women in 2002-2004 and 2012-2014. HEI, MDS and DQI were calculated. Waist circumference (WC) and Body Mass Index (BMI) were used as anthropometric parameters. A linear regression analysis was performed to investigate associations between changes in dietary indices and changes in respectively anthropometric parameters and blood lipids, adjusted for potential confounders. Results: Only in men an increase in all three dietary indices was associated with a decrease in WC and BMI in the non-adjusted analysis and for HEI and DQI also in the adjusted analysis. No longitudinal associations were found between dietary indices and blood lipids both in men and women. Conclusions: Only few associations were found between dietary indices and anthropometric parameters, whilst no associations were found with blood lipids. An increase in dietary indices was associated with an improvement in anthropometric parameters only in men. As this is the first study investigating associations between changes in dietary indices and changes in respectively anthropometric parameters and blood lipids, further research is needed to evaluate these possible associations. [ABSTRACT FROM AUTHOR]

Background: Cattle populations are characterized by regular outburst of genetic defects as a result of the extensive use of elite sires. The causative genes and mutations can nowadays be rapidly identified by means of genome-wide association studies combined with next generation DNA sequencing, provided that the causative mutations are conventional loss-of-function variants. We show in this work how the combined use of next generation DNA and RNA sequencing allows for the rapid identification of otherwise difficult to identify splice-site variants. Results: We report the use of haplotype-based association mapping to identify a locus on bovine chromosome 10 that underlies autosomal recessive arthrogryposis in Belgian Blue Cattle. We identify 31 candidate mutations by resequencing the genome of four cases and 15 controls at ~10-fold depth. By analyzing RNA-Seq data from a carrier fetus, we observe skipping of the second exon of the PIGH gene, which we confirm by RT-PCR to be fully penetrant in tissues from affected calves. We identify - amongst the 31 candidate variants - a C-to-G transversion in the first intron of the PIGH gene (c211-10C > G) that is predicted to affect its acceptor splice-site. The resulting PIGH protein is likely to be non-functional as it lacks essential domains, and hence to cause arthrogryposis. Conclusions: This work illustrates how the growing arsenal of genome exploration tools continues to accelerate the identification of an even broader range of disease causing mutations, therefore improving the management and control of genetic defects in livestock. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal nematodes are an important cause of reduced performance in cattle. Previous studies in Europe showed that after anthelmintic treatment an average gain in milk production of around 1 kg per day/ cow can be expected. However, (1) these studies have mainly evaluated group-based anthelmintic treatments during the grazing season or at housing and (2) little is known about parameters affecting variations in the treatment response amongst cows. A better knowledge of such parameters could help to select animals that benefit most from treatment and thus lead to a more rational use of anthelmintics. Therefore, a randomized, non-blinded, controlled clinical trial was performed on 11 commercial dairy farms (477 animals) in Belgium, aiming (1) to study the effect of eprinomectin treatment at calving on milk production and (2) to investigate whether the milk yield response was related to non-invasive animal parameters such that these could be used to inform targeted selective treatment decisions. Results: Analyses show that eprinomectin treatment around calving resulted in an average (± standard error) increase of 0.97 (±0.41) kg in daily milk yield that was followed up over 274 days on average. Milk yield responses were higher in multiparous compared to primiparous cows and in cows with a high (4th quartile) anti-O. ostertagi antibody level in a milk sample from the previous lactation. Nonetheless, high responses were also seen in animals with a low (1st quartile) anti-O. ostertagi antibody level. In addition, positive treatment responses were associated with higher faecal egg counts and a moderate body condition score at calving (2nd quartile). Conclusions: In conclusion, this study provides novel insights into the production response after anthelmintic treatment at calving and factors which influence this. The data could be used to support the development of evidence-based targeted selective anthelmintic treatment strategies in dairy cattle. [ABSTRACT FROM AUTHOR]

Background: The gastrointestinal nematode (GIN) Ostertagia ostertagi can cause severe disease in first season grazers (FSG) and impaired performance due to subclinical infections in adult cows. Diagnostic methods to assess exposure include faecal egg count and detection of specific antibodies using antibody-ELISAs resulting in an optical density ratio (ODR). Using the ELISA test on bulk tank milk (BTM) allows for a herd level diagnosis. Appropriate use of diagnostic methods for evaluation of O. ostertagi exposure is required to optimize herd parasite surveillance and aid in a sustainable control regime. The aim of this study was to describe the relationship between different diagnostic tests used to assess GIN exposure in Norwegian production systems. A cross-sectional field study was carried out in twenty herds in Norway in the fall of 2020. Serum and faecal samples were taken from 380 individuals, of which 181 were FSG and 199 were cows. In addition, milk was collected from every cow and one BTM sample was taken from each herd. Faecal egg counts were performed. The distribution of ODR values in individual samples within and between herds and the associations between BTM ODR and individual ODR values were described. The data were analysed using visual assessment of scatter plots, Pearson correlation coefficients and linear regression. Results: A high variability of the within-herd individual ODR values in serum and milk in every herd was detected. The ODR in BTM explained a low degree of the variation in the individual serum and milk samples. When plotting the ODR results in milk or serum according to four BTM categories, the distribution of ODR values were notably different in the highest and lowest BTM categories. The correlation between individual milk and serum samples was moderate (r = 0.68), while the highest correlation (r = 0.81) was between the BTM ODR and the group average individual milk samples. Conclusions: A poor predictive ability for BTM ODR to assess individual ODR values in both FSG and cows was demonstrated. However, the study indicates that the evaluation by ELISA test on BTM to assess exposure to GIN could be useful in herds with a very high or low BTM ODR. [ABSTRACT FROM AUTHOR]

Background: Antidepressants are often considered to be mere placebos despite the fact that meta-analyses are able to rank them. It follows that it should also be possible to rank different placebos, which are all made of sucrose. To explore this issue, which is rather more epistemological than clinical, we designed an unusual meta-analysis to investigate whether the effects of placebo in one situation are different from the effects of placebo in another situation. Methods: Published and unpublished studies were searched for by three reviewers on Medline, the Cochrane Library, Embase, clinicaltrials.gov, Current Controlled Trial, in bibliographies, and by mailing key organizations. The following studies in first-line treatment for major depressive disorder were considered to construct an "evidence network": 1) randomized controlled trials (RCTs) versus placebo on fluoxetine, venlafaxine and 2) fluoxetine versus venlafaxine head-to-head RCTs. Two network meta-analyses were run to indirectly compare response and remission rates among three different placebos: 1) fluoxetine placebo, 2) venlafaxine placebo, and 3) venlafaxine/fluoxetine placebo (that is, placebo compared to both venlafaxine and fluoxetine). Publication biases were assessed using funnel plots and statistically tested. Results: The three placebos were not significantly different in terms of response or remission. The antidepressant agents were significantly more efficacious than the placebos, and venlafaxine was more efficacious than fluoxetine. The funnel plots, however, showed a major publication bias. Conclusion: The presence of significant levels of publication bias indicates that we cannot even be certain of the conclusion that sucrose equals sucrose in trials of major depressive disorder. This result should remind clinicians to step back to take a more objective view when interpreting a scientific result. It is of crucial importance for their practice, far more so than ranking antidepressant efficacy. [ABSTRACT FROM AUTHOR]

Background: The public and private sector in the EU spend around €800 million per year on animal health and welfare related research. An objective process to identify critical gaps in knowledge and available control tools should aid the prioritisation of research in order to speed up the development of new or improved diagnostics, vaccines and pharmaceuticals and reduce the burden of animal diseases. Method: Here, we describe the construction of a database based on expert consultation for 52 infectious diseases of animals. Results: For each disease, an expert group produced a disease and product analysis document that formed the basis for gap analysis and prioritisation. The prioritisation model was based on a closed scoring system, employing identical weights for six evaluation criteria (disease knowledge; impact on animal health and welfare; impact on public health; impact on wider society; impact on trade; control tools). The diseases were classified into three groups: epizootic diseases, food-producing animal complexes or zoonotic diseases. Discussion: The highly ranked diseases in the prioritisation model comprised mostly zoonotic and epizootic diseases with important gaps identified in vaccine development and pharmaceuticals, respectively. The most important outcome is the identification of key research needs by disease. The rankings and research needs by disease are provided on a public website (www.discontools.eu) which is currently being updated based on new expert consultations. Conclusion: As such, it can become a reference point for funders of research including the European Commission, member states, foundations, trusts along with private industry to prioritise research. This will deliver benefits in terms of animal health and welfare but also public health, societal benefits and a safe and secure food supply. [ABSTRACT FROM AUTHOR]

Background: On-line provision of information during the transition phase after treatment carries great promise in meeting shortcomings in post-treatment care for breast cancer survivors and their partners. The objectives of this study are to describe the development and process evaluation of a tailored informative website and to assess which characteristics of survivors and partners, participating in the feasibility study, are related to visiting the website. Methods: The development process included quantitative and qualitative assessments of survivors' and partners' care needs and preferences. Participants' use and evaluation of the website were explored by conducting baseline and post-measurements. During the intervening 10-12 weeks 57 survivors and 28 partners were granted access to the website. Results: Fifty-seven percent (n=21) of survivors who took part in the post-measurement indicated that they had visited the website. Compared to non-visitors (n=16), they were more likely to have a partner and a higher income, reported higher levels of self-esteem and had completed treatment for a longer period of time. Partners who consulted the on-line information (42%, n=8) were younger and reported lower levels of social support compared to partners who did not visit the website (n=11). Visitors generally evaluated the content and lay-out positively, yet some believed the information was incomplete and impersonal. Conclusions: The website reached only about half of survivors and partners, yet was mostly well-received. Besides other ways of providing information and support, a website containing clear-cut and tailored information could be a useful tool in post-treatment care provision. [ABSTRACT FROM AUTHOR]

Background: On-line provision of information during the transition phase after treatment carries great promise in meeting shortcomings in post-treatment care for breast cancer survivors and their partners. The objectives of this study are to describe the development and process evaluation of a tailored informative website and to assess which characteristics of survivors and partners, participating in the feasibility study, are related to visiting the website. Methods: The development process included quantitative and qualitative assessments of survivors' and partners' care needs and preferences. Participants' use and evaluation of the website were explored by conducting baseline and post-measurements. During the intervening 10-12 weeks 57 survivors and 28 partners were granted access to the website. Results: Fifty-seven percent (n=21) of survivors who took part in the post-measurement indicated that they had visited the website. Compared to non-visitors (n=16), they were more likely to have a partner and a higher income, reported higher levels of self-esteem and had completed treatment for a longer period of time. Partners who consulted the on-line information (42%, n=8) were younger and reported lower levels of social support compared to partners who did not visit the website (n=11). Visitors generally evaluated the content and lay-out positively, yet some believed the information was incomplete and impersonal. Conclusions: The website reached only about half of survivors and partners, yet was mostly well-received. Besides other ways of providing information and support, a website containing clear-cut and tailored information could be a useful tool in post-treatment care provision. [ABSTRACT FROM AUTHOR]

Background: Gene expression is regulated through a complex interplay of different transcription factors (TFs) which can enhance or inhibit gene transcription. ArcA is a global regulator that regulates genes involved in different metabolic pathways, while IclR as a local regulator, controls the transcription of the glyoxylate pathway genes of the aceBAK operon. This study investigates the physiological and metabolic consequences of arcA and iclR deletions on E. coli K12 MG1655 under glucose abundant and limiting conditions and compares the results with the metabolic characteristics of E. coli BL21 (DE3). Results: The deletion of arcA and iclR results in an increase in the biomass yield both under glucose abundant and limiting conditions, approaching the maximum theoretical yield of 0.65 c-mole/c-mole glucose under glucose abundant conditions. This can be explained by the lower flux through several CO2 producing pathways in the E. coli K12 ΔarcAΔiclR double knockout strain. Due to iclR gene deletion, the glyoxylate pathway is activated resulting in a redirection of 30% of the isocitrate molecules directly to succinate and malate without CO2 production. Furthermore, a higher flux at the entrance of the TCA was noticed due to arcA gene deletion, resulting in a reduced production of acetate and less carbon loss. Under glucose limiting conditions the flux through the glyoxylate pathway is further increased in the ΔiclR knockout strain, but this effect was not observed in the double knockout strain. Also a striking correlation between the glyoxylate flux data and the isocitrate lyase activity was observed for almost all strains and under both growth conditions, illustrating the transcriptional control of this pathway. Finally, similar central metabolic fluxes were observed in E. coli K12 ΔarcA ΔiclR compared to the industrially relevant E. coli BL21 (DE3), especially with respect to the pentose pathway, the glyoxylate pathway, and the TCA fluxes. In addition, a comparison of the genome sequences of the two strains showed that BL21 possesses two mutations in the promoter region of iclR and rare codons are present in arcA implying a lower tRNA acceptance. Both phenomena presumably result in a reduced ArcA and IclR synthesis in BL21, which contributes to the similar physiology as observed in E. coli K12 ΔarcAΔiclR. Conclusions: The deletion of arcA results in a decrease of repression on transcription of TCA cycle genes under glucose abundant conditions, without significantly affecting the glyoxylate pathway activity. IclR clearly represses transcription of glyoxylate pathway genes under glucose abundance, a condition in which Crp activation is absent. Under glucose limitation, Crp is responsible for the high glyoxylate flux, but IclR still represses transcription. Finally, in E. coli BL21 (DE3), ArcA and IclR are poorly expressed, explaining the similar fluxes observed compared to the ΔarcAΔiclR strain. [ABSTRACT FROM AUTHOR]

Background: When heterologous recombinant proteins are produced in Escherichia coli, they often precipitate to form insoluble aggregates of unfolded polypeptides called inclusion bodies. These structures are associated with chaperones like IbpA. However, there are reported cases of "non-classical" inclusion bodies in which proteins are soluble, folded and active. Results: We report that the Brucella abortus PdhS histidine kinase fused to the mCherry fluorescent protein forms intermediate aggregates resembling "non-classical" inclusion bodies when overproduced in E. coli, before forming "classical" inclusion bodies. The intermediate aggregates of PdhS-mCherry are characterized by the solubility of PdhS-mCherry, its ability to specifically recruit known partners fused to YFP, suggesting that PdhS is folded in these conditions, and the quick elimination (in less than 10 min) of these structures when bacterial cells are placed on fresh rich medium. Moreover, soluble PdhS-mCherry foci do not systematically colocalize with IpbA-YFP, a marker of inclusion bodies. Instead, time-lapse experiments show that IbpA-YFP exhibits rapid pole-to-pole shuttling, until it partially colocalizes with PdhS-mCherry aggregates. Conclusion: The data reported here suggest that, in E. coli, recombinant proteins like PdhS-mCherry may transit through a soluble and folded state, resembling previously reported "non-classical" inclusion bodies, before forming "classical" inclusion bodies. The dynamic localization of IbpA-YFP foci suggests that the IbpA chaperone could scan the E. coli cell to find its substrates. [ABSTRACT FROM AUTHOR]

Background: Chronic exposure to mild irritants including cleansing and antiseptic products used for hand hygiene generates insults to the skin. To avoid unpleasant reactions, skin protection creams are commonly employed, but some fail to afford protection against a variety of xenobiotics. In this study, two skin protection creams were assayed comparatively looking for a protective effect if any against a liquid soap and an alcohol-based gel designed for hand hygiene in medical settings. Methods: Corneosurfametry and corneoxenometry are two in vitro bioessays which were selected for their good reproducibility, sensitivity and ease of use. A Kruskal-Wallis ANOVA test followed by the Dunn test was realized to compare series of data obtained. Results: Significant differences in efficacy were obtained between the two assayed skin protection creams. One of the two tested creams showed a real protective effect against mild irritants, but the other tested cream presented an irritant potential in its application with mild irritants. Conclusion: The differences observed for the two tested skin protection creams were probably due to their galenic composition and their possible interactions with the offending products. As a result, the present in vitro bioassays showed contrasted effects of the creams corresponding to either a protective or an irritant effect on human stratum corneum. [ABSTRACT FROM AUTHOR]

Background: The variability in the inflammatory burden of the lung in cystic fibrosis (CF) patients together with the variable effect of glucocorticoid treatment led us to hypothesize that glucocorticoid receptor (GR) gene polymorphisms may affect glucocorticoid sensitivity in CF and, consequently, may contribute to variations in the inflammatory response. Methods: We evaluated the association between four GR gene polymorphisms, TthIII, ER22/23EK, N363S and BclI, and disease progression in a cohort of 255 young patients with CF. Genotypes were tested for association with changes in lung function tests, infection with Pseudomonas aeruginosa and nutritional status by multivariable analysis. Results: A significant non-corrected for multiple tests association was found between BclI genotypes and decline in lung function measured as the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). Deterioration in FEV1 and FVC was more pronounced in patients with the BclI GG genotype compared to the group of patients with BclI CG and CC genotypes (p = 0.02 and p = 0.04 respectively for the entire cohort and p = 0.01 and p = 0.02 respectively for F508del homozygous patients). Conclusion: The BclI polymorphism may modulate the inflammatory burden in the CF lung and in this way influence progression of lung function. [ABSTRACT FROM AUTHOR]

Lactococcus lactis, the model lactic acid bacterium (LAB), is a food grade and well-characterized Gram positive bacterium. It is a good candidate for heterologous protein delivery in foodstuff or in the digestive tract. L. lactis can also be used as a protein producer in fermentor. Many heterologous proteins have already been produced in L. lactis but only few reports allow comparing production yields for a given protein either produced intracellularly or secreted in the medium. Here, we review several works evaluating the influence of the localization on the production yields of several heterologous proteins produced in L. lactis. The questions of size limits, conformation, and proteolysis are addressed and discussed with regard to protein yields. These data show that i) secretion is preferable to cytoplasmic production; ii) secretion enhancement (by signal peptide and propeptide optimization) results in increased production yield; iii) protein conformation rather than protein size can impair secretion and thus alter production yields; and iv) fusion of a stable protein can stabilize labile proteins. The role of intracellular proteolysis on heterologous cytoplasmic proteins and precursors is discussed. The new challenges now are the development of food grade systems and the identification and optimization of host factors affecting heterologous protein production not only in L. lactis, but also in other LAB species. [ABSTRACT FROM AUTHOR]

Background: Airborne pollution is a rising concern in urban areas. Epidemiological studies in humans and animal experiments using rodent models indicate that gestational exposure to airborne pollution, in particular diesel engine exhaust (DE), reduces birth weight, but effects depend on exposure duration, gestational window and nanoparticle (NP) concentration. Our aim was to evaluate the effects of gestational exposure to diluted DE on feto-placental development in a rabbit model. Pregnant females were exposed to diluted (1 mg/m3), filtered DE (NP diameter ≈ 69 nm) or clean air (controls) for 2 h/day, 5 days/week by nose-only exposure (total exposure: 20 days in a 31-day gestation). Results: DE exposure induced early signs of growth retardation at mid gestation with decreased head length (p = 0.04) and umbilical pulse (p = 0.018). Near term, fetal head length (p = 0.029) and plasma insulin and IGF1 concentrations (p = 0.05 and p = 0.019) were reduced. Placental function was also affected, with reduced placental efficiency (fetal/placental weight) (p = 0.049), decreased placental blood flow (p = 0.009) and fetal vessel volume (p = 0.002). Non-aggregated and "fingerprint" NP were observed at various locations, in maternal blood space, in trophoblastic cells and in the fetal blood, demonstrating transplacental transfer. Adult female offspring were bred with control males. Although fetoplacental biometry was not affected near term, second generation fetal metabolism was modified by grand-dam exposure with decreased plasma cholesterol (p = 0.008) and increased triglyceride concentrations (p = 0.015). Conclusions: Repeated daily gestational exposure to DE at levels close to urban pollution can affect feto-placental development in the first and second generation. [ABSTRACT FROM AUTHOR]

Background: A major constraint for the effective control and management of helminth parasites is the lack of rapid, high-throughput, routine diagnostic tests to assess the health status of individual animals and herds and to identify the parasite species responsible for these helminthoses. The capability of a multiplex platform for the simultaneous detection of three pasture associated parasite species was evaluated and compared to existing ELISAs. Methods: The recombinant antigens 14.2 kDa ES protein for Cooperia oncophora, major sperm protein for Dictyocaulus viviparus and Cathepsin L1 for Fasciola hepatica were recombinantly expressed either in Escherichia coli or Pichia pastoris. Antigens were covalently coupled onto magnetic beads. Optimal concentrations for coupling were determined following the examination of serum samples collected from experimentally mono-infected animals, before and after their infection with the target species. Absence of cross-reactivity was further determined with sera from calves mono-infected with Haemonchus contortus, Ostertagia ostertagi and Trichostrongylus colubriformis. Examination of negative serum samples was characterised by low median fluorescence intensity (MFI). Results: Establishment of the optimal serum dilution of 1:200 was achieved for all three bead sets. Receiver Operating Characteristic analyses were performed to obtain cut-off MFI values for each parasite separately. Sensitivity and specificity at the chosen cut-off values were close to, or 100 % for all bead sets. Examination of serum samples collected on different days post infection from different animals showed a high reproducibility of the assays. Serum samples were additionally examined with two already established ELISAs, an in-house ELISA using the recombinant MSP as an antigen and a DRG ELISA using Cathepsin L1 for liver fluke. The results between the assays were compared and kappa tests revealed an overall good agreement. Conclusions: A versatile bead-based assay using fluorescence detection (xMAP® technology) was developed to simultaneously detect antibodies against C. oncophora, D. viviparus and F. hepatica in cattle serum samples. This platform provides rapid, high-throughput results and is highly sensitive and specific in comparison to existing serological as well as coproscopical diagnostic techniques. [ABSTRACT FROM AUTHOR]